Histocompatibility genes code for cell membrane components involved in immune response regulation. This is evidenced by the association of histocompatibility phenotype and incidence of transplantation immunity, specific immune responsiveness to certain antigens and their pathological counterparts, susceptibility to neoplastic and immune diseases. Since it became increasingly clear that all species including man, display a general similarity with respect to their histocompatibility antigen system, genetically-defined animal models are the most suited to investigate the genetic fine structure, gene action, gene regulation and gene evolution of this system, specifically in respect to the peculiarities of cell differentiation leading to immunocompetence and its deviations. The major efforts of this proposal are 1) to improve the possibility of investigating the genetic basis and functional aspects of these phenomena by continuation of production of specifically-needed congenic rat lines; 2) the search for and selection of recombinants regarding cell membrane antigens and functionally recognizable traits such as mixed lymphocyte culture reaction, immune responsiveness, and susceptibility to disease; and 3) to elucidate the serological, biological and molecular properties of gene products regulating immune responsiveness in rats and mice.